Targeting vascular smooth muscle cells with natural compounds to combat atherosclerosis

Atherosclerosis (AS) is widely recognized as the principal pathological substrate underlying chronic cardiovascular diseases (CVDs). It is a chronic, progressive, and inflammatory disease characterized by excessive lipid deposition, oxidative stress, inflammatory response, plaque formation and rupture, thrombosis and vascular calcification (VC). Vascular smooth muscle cells (VSMCs) are essential for maintaining the normal structure of blood vessels and play a pivotal role in the pathological process of AS. Their proliferation, migration, differentiation, senescence and death processes critically influence the progression of AS. The specific mechanism of VSMCs participating in AS remains a central focus of research in the cardiovascular field. In recent years, natural products have garnered considerable attention in the field of AS prevention and treatment, primarily due to their multi-target effects, low toxicity and side effects. However, there is still a lack of systematic review of natural compounds that alleviate AS by regulating the function of VSMCs. This article focuses on the core role of VSMCs in the progression of AS, and systematically reviews the natural compounds targeting VSMCs metabolism and their molecular regulatory mechanisms. By combing the relevant pharmacological activities and potential targets, the pathological function of VSMCs in AS is further elucidated, thereby providing an important theoretical basis for the development of novel and efficient AS treatment strategies.